Studies on ergot alkaloids will be continued along the following lines: 1) Completion of ongoing studies on the stereochemical course of the isoprenylation of tryptophan, on the mode of formation of the alpha-hydroxyamino acid moiety of the peptide ergot alkaloids, on the synthesis of "D-ring inverted" ergoline analogs and on the induction and feedback inhibition of ergot alkaloid biosynthesis. 2) Clarification of the chemistry involved in the biosynthetic formation of ring C of the ergolines. 3) Enzymology of D-ring formation. 4) Enzymology of peptide ergot alkaloid formation. 5) Chemical and biochemical functionalization of ring A to generate more potent dopamine agonists and/or tumor inhibitors, and biomimetic chemical closure of ring C.